Chronic Hepatitis D InfectionPhase 2LOWR-1NCT02430181
Lonafarnib With and Without Ritonavir in HDV (LOWR-1)
A Phase 2 study testing lonafarnib, peginterferon alfa-2a and ritonavir in people with Chronic Hepatitis D Infection, run by EIT Pharma, Inc. at 1 site in Turkey (Türkiye).
Trial summary
To Evaluate the Safety and Efficacy of Lonafarnib with and without Ritonavir Boosting in Adults With Genotype 1 Chronic Hepatitis D Virus (HDV) Infection (LOWR-1). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis D Infection
- What is being tested?
- lonafarnib, peginterferon alfa-2a and ritonavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- Nov 2014to Nov 2015
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR
- Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry
- Liver biopsy within the last two years
- Positive viral load by quantitative PCR
- Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval <450 milliseconds - using Bazett's correction
- Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study:
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- abstinence
- surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum
- IUD in place for at least six months
- barrier methods (condom or diaphragm) with spermicide
- surgical sterilization of the partner (vasectomy for six months)
- hormonal contraceptives for at least three months prior to the first dose of study drug
- Willing and able to comply with study procedures and provide written informed consent
Who cannot join
- Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1
- Patients co-infected with HIV
- Patients with screening tests positive for HCV, or anti-HIV Ab
- History of decompensated cirrhosis within the past year
- Active jaundice defined by total bilirubin > 2.0 excluding Gilbert's disease
- INR ≥ 1.5
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- Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (> 20 g per day for females (1.5 standard alcohol drinks) or > 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL).
- Drug abuse within the last six months with the exception of cannabinoids and their derivatives
- Patients with absolute neutrophil count (ANC) < 1500 cells/mm^3; platelet count < 100,000 cells/mm^3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN)
- History or clinical evidence of any of the following:
- variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6, decompensated liver disease or any other form of non-viral hepatitis
- immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent nonsteroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed)
- any malignancy within 3 years except for basal cell skin cancer
- significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
- chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
- severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization 2
- Patients with a body mass index > 30 kg/m^2
- Concomitant drugs known to prolong the QT interval
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With and Without Ritonavir Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-1)
To Evaluate the Safety and Efficacy of Lonafarnib with and without Ritonavir Boosting in Adults With Genotype 1 Chronic Hepatitis D Virus (HDV) Infection (LOWR-1).
Read the detailed description
Chronic delta hepatitis is a serious form of chronic liver disease caused by infection with the hepatitis D virus (HDV), a small RNA virus that requires farnesylation of its major structural protein (HDV antigen) for replication. Twenty-one subjects with chronic delta hepatitis will be randomized to receive one of seven different doses of lonafarnib. Dosing will occur over 4-12 weeks, depending on treatment arm, and during that time, evidence of antiviral response will be assessed by frequent measurements of HDV-RNA. The primary therapeutic endpoint will be an improvement in quantitative serum HDV RNA levels after treatment with lonafarnib therapy. The primary safety endpoint will be the ability to tolerate the drug at the prescribed dose for the treatment duration. Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms. Therapy will be stopped for intolerance to lonafarnib. This study is designed as a phase 2a study assessing the safety, tolerance and antiviral activity of seven dose combinations of lonafarnib with and without ritonavir boosting.
- Conditions
- Chronic Hepatitis D Infection
- Being tested
- lonafarnib, peginterferon alfa-2a, ritonavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lonafarnibDrug
Also called Sarasar, EBP994
antiviral farnesyl transferase inhibitor
peginterferon alfa-2aDrug
Also called Pegasys, pegylated interferon-alfa, PEG IFN-alfa, PEG IFN-a
immunomodulator
ritonavirDrug
Also called Norvir, RTV
CYP 3A4 inhibitor, lonafarnib booster
| Study group | Role | What they receive |
|---|---|---|
| lonafarnib - I | Experimental | lonafarnib 200 mg BID; n=3 Receives: Drug: lonafarnib |
| lonafarnib - II | Experimental | lonafarnib 300 mg BID; n=3 Receives: Drug: lonafarnib |
| lonafarnib - III | Experimental | lonafarnib 100 mg TID; n=3 Receives: Drug: lonafarnib |
| lonafarnib/PEG IFN-a - I | Experimental | lonafarnib 100 mg BID + PEG IFN-a 180 ug QW; n=3 Receives: Drug: lonafarnib; Drug: peginterferon alfa-2a |
| lonafarnib/PEG IFN-a - II | Experimental | lonafarnib 200 mg BID + PEG IFN-a 180 ug QW; n=3 Receives: Drug: lonafarnib; Drug: peginterferon alfa-2a |
| lonafarnib/PEG IFN-a - III | Experimental | lonafarnib 300 mg BID + PEG IFN-a 180 ug QW; n=2 Receives: Drug: lonafarnib; Drug: peginterferon alfa-2a |
| lonafarnib/ritonavir | Experimental | lonafarnib 100 mg BID + ritonavir 100 mg QD; n=3 Receives: Drug: lonafarnib; Drug: ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Quantitative Serum HDV RNA Levels After 4-12 Weeks of Lonafarnib-based Therapy
log HDV RNA decline from baseline to end of treatment (4-12 weeks of lonafarnib-based therapy)
Measured: 4-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2015 (estimated)
- Study startNov 2014
- Primary completionSep 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis D InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- EIT Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cihan Yurdaydin, MD, Principal investigator, Ankara University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02430181
- Sponsor's protocol ID
- EIG-300
- Other IDs
- Application #1128309
- Acronym
- LOWR-1
- Status last verified
- Nov 2022
- First submitted
- 21 Apr 2015
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No